Comorbidities predict inferior outcomes in chronic lymphocytic leukemia treated with ibrutinib.

BACKGROUND: Most patients with chronic lymphocytic leukemia (CLL) present with multiple comorbidities. Although comorbidities negatively affect outcomes for patients treated with chemoimmunotherapy, their impact on patients who receive targeted therapies is unknown. METHODS: This multicenter, retrospective analysis evaluated the significance of comorbidities, as assessed by the Cumulative Illness Rating Scale (CIRS), among patients with CLL treated with ibrutinib. RESULTS: One hundred forty-five patients received ibrutinib (80% in a relapsed/refractory setting). A high burden of comorbidities (CIRS score ≥ 7) was associated with inferior median event-free survival (EFS; 24 vs 37 months; P = .003) and 2-year overall survival (OS; 79% vs 100%; P = .005). In an adjusted Cox model, both EFS and OS worsened with an incremental increase in the CIRS score. Furthermore, comorbidities were associated with an increased risk of ibrutinib dose reduction and therapy discontinuation. CIRS was predictive in both frontline and relapsed CLL, regardless of patient age. CONCLUSIONS: Comorbidities portend a poor prognosis among patients with CLL treated with ibrutinib. Prospective studies are needed to optimize the treatment of patients with CLL who have comorbidities. Cancer 2018. © 2018 American Cancer Society.

Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry.

BACKGROUND AND AIMS: Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients. METHODS: We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance. RESULTS: In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90). CONCLUSIONS: In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.

Risk Factors for Mortality Among Individuals With Peripheral Arterial Disease.

Morbidity and mortality from peripheral arterial disease (PAD) continues to increase. Traditional cardiovascular risk factors are implicated in the development of PAD, yet the extent to which those risk factors correlate with mortality in such patients remains insufficiently assessed. Using data from the 1999 to 2004 National Health and Nutrition Examination Survey, Cox proportional hazards models were used to examine the association of cardiovascular risk factors and all-cause and cardiovascular mortality. A total of 647 individuals ≥40 years old with PAD (i.e., ankle-brachial index [ABI] ≤ 0.9) were followed for a median of 7.8 years. There were 336 deaths, of which 98 were attributable to cardiovascular disease. Compared with never smokers, current (hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.62 to 3.71) and former (HR 1.62, 95% CI 1.14 to 2.29) smokers with PAD had higher rates of death. Moderate or vigorous physical activity of ≥10 minutes monthly was associated with lower death rates (HR 0.63, 95% CI 0.44 to 0.91). Also associated with increased rates of cardiovascular death were an ABI of <0.5 (HR 2.56, 95% CI 1.28 to 5.15, compared with those with an ABI of 0.7 to 0.9) and diabetes mellitus (HR 2.50, 95% CI 1.33 to 4.73). Neither C-reactive protein nor body mass index was associated with mortality. In conclusion, tobacco use increased the risk of all-cause and cardiovascular death, whereas physical activity was associated with a decreased mortality risk. A low ABI and diabetes were also predictive of cardiovascular death.

Health Effects of Overweight and Obesity in 195 Countries over 25 Years.

BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015. RESULTS: In 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease. CONCLUSIONS: The rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.).

Perceptions of e-Cigarettes and Noncigarette Tobacco Products Among US Youth.

BACKGROUND: Electronic cigarettes (e-cigarettes) are now the most commonly used tobacco product among US youth. The extent to which perceptions of e-cigarettes' harm and addictiveness differ from those of other products remains unknown, as does whether these perceptions have changed over time. METHODS: Data from the 2012 and 2014 National Youth Tobacco Survey, a repeated cross-sectional survey of grade 6 to 12 students, were used. Cross-tabulations and logistic regression models were used to describe correlates of perceptions of harm and addictiveness of e-cigarettes, cigars, and smokeless tobacco compared with cigarettes. Trends in perceptions of e-cigarettes' harm among different demographic groups were also assessed. RESULTS: In 2014, 73.0% believed that e-cigarettes were less harmful than cigarettes, compared with 20.2% for smokeless tobacco and 25.8% for cigars. By comparison, 47.1% believed that e-cigarettes were less addictive than cigarettes, compared with only 14.0% for smokeless tobacco and 31.5% for cigars. Use of each product was associated with a perception of decreased harm and addictiveness in adjusted analyses, as was being male, being a non-Hispanic white, and residing with a household member who used that product. Between 2012 and 2014, increasing numbers of US youth thought they were able to assess the relative harm of e-cigarettes and increasingly believed that e-cigarettes are less harmful than cigarettes. CONCLUSIONS: Most US youth view e-cigarettes as less harmful and addictive than cigarettes. Far fewer think similarly about cigars and smokeless tobacco. Increases in e-cigarettes' perceived safety mirrors rapid increases observed in their use. Perceived safety correlates with use of each tobacco product.

Multiple biomarkers for mortality prediction in peripheral arterial disease.

Few studies have assessed which biomarkers influence mortality risk among those with peripheral arterial disease (PAD). We analyzed data from 556 individuals identified to have PAD (i.e. ankle-brachial index ⩽ 0.9) with available measurements of C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), homocysteine, and the urinary albumin-to-creatinine ratio (UACR) in the 1999-2004 National Health and Nutrition Examination Survey. We investigated whether a combination of these biomarkers improved the prediction of all-cause and cardiovascular mortality beyond conventional risk factors. During follow-up (median, 8.1 years), 277 of 556 participants died; 63 deaths were attributed to cardiovascular disease. After adjusting for conventional risk factors, Cox proportional-hazards models showed the following to be most strongly associated with all-cause mortality (each is followed by the adjusted hazard ratio [HR] per 1 standard deviation increment in the log values): homocysteine (1.31), UACR (1.21), and NLR (1.20). UACR alone significantly predicted cardiovascular mortality (1.53). Persons in the highest quintile of multimarker scores derived from regression coefficients of significant biomarkers had elevated risks of all-cause mortality (adjusted HR, 2.45; 95% CI, 1.66-3.62; p for trend, <0.001) and cardiovascular mortality (adjusted HR, 2.20; 95% CI, 1.02-4.71; p for trend, 0.053) compared to those in the lowest two quintiles. The addition of continuous multimarker scores to conventional risk factors improved risk stratification of all-cause mortality (integrated discrimination improvement [IDI], 0.162; p<0.00001) and cardiovascular mortality (IDI, 0.058; p<0.00001). In conclusion, the addition of a continuous multimarker score to conventional risk factors improved mortality prediction among patients with PAD.

Passive and Active Tobacco Exposure and Children's Lipid Profiles.

INTRODUCTION: Despite reductions in smoking rates, exposure to cigarette smoke remains common among US children and adolescents. In adults, active smoking and secondhand smoke (SHS) exposure have been linked to adverse changes in lipid profiles and increases in inflammatory markers. Evidence that such changes are present before adulthood remains limited, and the extent to which active smoking and SHS exposure affect these cardiovascular measures in children has not been thoroughly assessed. METHODS: We employed data from 2008 individuals aged 12-19 years from the 2005-2010 National Health and Nutrition Examination Survey. Comparisons of the lipid and inflammatory marker levels among active smokers, those exposed to SHS (as determined by serum cotinine levels), and those unexposed to tobacco smoke were made using linear regression with multiple propensity score adjustment. RESULTS: Compared to unexposed children, lipid and inflammatory marker profiles did not differ among those exposed to SHS exposure. Among active smokers, differences compared to unexposed children were observed in triglyceride levels ( ß=8.5 mg/dL, P = .01), the ratio of triglycerides to high-density lipoprotein ( ß=0.2, P = .045), and low-density lipoprotein cholesterol ( ß=-4.1 mg/dL , P = .03), though these did not reach levels of confirmatory statistical significance. CONCLUSIONS: After accounting for sociodemographic characteristics and medical comorbidities, serum lipids and markers of systemic inflammation were not associated with SHS exposure. Tobacco smoke exposure in children may require longer durations of compounded effect before serum lipid abnormalities are detected. IMPLICATIONS: This paper adds detail to the study of secondhand smoke's effects on lipid profiles of children and adolescents. Prior research on this topic for these age groups has been limited, and this study provides national, cross-sectional data to show that both secondhand smoke and active smoking in childhood and adolescence is not associated with changes in lipid profiles or markers of inflammation. Tobacco smoke exposure may require longer durations of compounded effect before abnormalities are detected.

Adolescents' perceptions of light and intermittent smoking in the United States.

BACKGROUND: Light smoking, consuming a few cigarettes daily, and intermittent, or nondaily, smoking patterns are increasingly common but carry health risks comparable to heavier smoking patterns. Nearly all smokers begin smoking as adolescents, who are at risk for developing these smoking patterns. Previous research suggests that smokers underestimate the risks associated with smoking. The extent to which adolescents perceive light and intermittent smoking as harmful has not been previously assessed. METHODS: Data from 24,658 US adolescents sampled by the 2012 National Youth Tobacco Survey, a national, school-based, cross-sectional survey, were examined. Cross-tabulations and multivariate ordered probit regression models were constructed to describe correlates of US adolescents' perception of light and intermittent smoking. RESULTS: Although most adolescents (88.0%; 95% confidence interval [CI], 87.2% to 88.8%) reported beliefs that a heavier smoking pattern is very harmful, only 64.3% (95% CI; 63.2% to 65.3%) and 33.3% (95% CI; 32.0% to 34.6%) reported that light and intermittent smoking, respectively, are very harmful. Conversely, nearly one-quarter of US adolescents believed intermittent smoking causes little or no harm. Males, younger adolescents, Hispanics, and non-Hispanic blacks were more likely than their peers to view light and intermittent smoking patterns as less harmful. Those who were already light or intermittent smokers, those who used other tobacco products, and those who had a family member who used tobacco were also less likely to view their smoking patterns as harmful. CONCLUSIONS: Misconceptions about the safety of light and intermittent smoking are widespread among US adolescents. Significant public health attention is needed to redress these misperceptions.

Perception of e-cigarette harm and its correlation with use among U.S. adolescents.

INTRODUCTION: U.S. adolescents increasingly use e-cigarettes. The perceived harm of e-cigarettes has not been described, nor has the correlation between harm perception and e-cigarette use been assessed. This study examines correlates of e-cigarette harm perception and use of e-cigarettes in a national survey. METHODS: We used cross-sectional nationally representative data from the 2012 National Youth Tobacco Survey (n = 24,658). Cross-tabulations and multivariate ordered probit and logistic regression models were employed to assess relative harm perception and e-cigarette use. RESULTS: Half of U.S. adolescents had heard of e-cigarettes. Of these, 13.2% (95% confidence interval [CI] = 11.7-14.9) and 4.0% (95% CI = 3.4-4.7) reported ever or currently using e-cigarettes, respectively. Of those aware of e-cigarettes, 34.2% (95% CI = 32.8-35.6) believed e-cigarettes were less harmful than cigarettes. Among those trying e-cigarettes, 71.8% (95% CI = 69.0-74.5) believed e-cigarettes were comparatively less harmful. Females and those ≥ 17 years old were more likely to perceive e-cigarettes as more harmful relative to cigarettes, while on average Whites, users of other tobacco products, and those with family members who used tobacco were more likely to perceive e-cigarettes as comparatively safer. Among cigarette-naive e-cigarette users, use of other tobacco products and perceived harm reduction by e-cigarettes were, respectively, on average associated with 1.6 and 4.1 percentage-point increases in e-cigarette use. CONCLUSIONS: Perception of e-cigarettes as less harmful than conventional cigarettes was associated with increased e-cigarette use, including among cigarette-naive e-cigarette users. These findings should prompt further scientific investigation and merit attention from regulators.

Effect of increased leptin and C-reactive protein levels on mortality: results from the National Health and Nutrition Examination Survey.

OBJECTIVE: Leptin and C-reactive protein (CRP) have each been linked to adverse cardiovascular events, and prior cross-sectional research suggests that increased levels of both biomarkers pose an even greater risk. The effect of increased levels of both leptin and CRP on mortality has not, however, been previously assessed. METHODS: We used data from the third National Health and Nutrition Examination Survey (NHANES III) to estimate the mortality effect of high leptin and high CRP levels. Outcomes were compared with the use of inverse-probability-weighting adjustment. Among 6259 participants included in the analysis, 766 were in their sex-specific, population-weighted highest quartiles of both leptin and CRP. Median follow-up time was 14.3 years. RESULTS: There was no significant difference in adjusted all-cause mortality between the groups (risk ratio 1.22, 95% confidence interval [CI], 0.97-1.54). Similar results were noted with the use of several different analytic methods and in many subgroups, though high leptin and CRP levels may increase all-cause mortality in males (hazard ratio, 1.80, 95% CI, 1.32-2.46; P for interaction, 0.011). A significant difference in cardiovascular mortality was also noted (risk ratio, 1.54, 95% CI, 1.08-2.18), though that finding was not confirmed in all sensitivity analyses.. CONCLUSIONS: In this observational study, no significant difference in overall all-cause mortality rates in those with high leptin and high CRP levels was found, though high leptin and CRP levels appear associated with increased mortality in males. High leptin and CRP levels also likely increase risk for cardiovascular death..

Parental psychological distress and children's mental health: results of a national survey.

OBJECTIVE: Questions persist as to which dimensions of child mental health are most associated with parental mental health status and if these associations differ by parental gender. We assessed associations between parental psychological distress and children's mental health. METHODS: Pooled data from the 2001, 2002, and 2004 National Health Interview Surveys (NHIS), a nationally representative, cross-sectional survey of US children aged 4 to 17 (n = 21,314), were used. Multivariate logistic regression was performed assessing associations between parental psychological distress, measured by the Kessler 6 scale, and the extended-form Strengths and Difficulties Questionnaire (SDQ) scales. RESULTS: Logistic regression demonstrated associations between parental psychological distress and increased likelihood of child mental health problems. Children aged 4 to 11 were more likely to have mental health problems if they had a psychologically distressed father (odds ratio [OR] 7.5, 95% confidence interval [CI] 2.3-24.3) or mother (OR 6.7, 95% CI 2.7-16.7). Children aged 12 to 17 with a psychologically distressed father (OR 4.53, 95% CI 1.18-17.47) or mother (OR 3.90, 95% CI 1.34-11.37) were also more likely than those without to have mental health problems. In parents of both genders, associations existed between parental psychological distress, and abnormal emotional symptoms in younger children, conduct disorder in older children, and hyperactivity in children of all ages. CONCLUSIONS: Parental psychological distress appears similarly associated with adverse child mental health outcomes, regardless of parental gender. These findings corroborate limited prior research and demonstrate that associations between child mental health and parental mental illness are similar in magnitude for fathers and mothers.

Adolescent indoor tanning use and unhealthy weight control behaviors.

OBJECTIVE: Youth indoor tanning rates remain high despite the potential for increased melanoma risk. No previous study has assessed the prevalence of unhealthy weight control behaviors in both male and female adolescent indoor tanning users using a nationally representative survey. METHODS: Pooled data on high school students from the 2009 and 2011 Youth Risk Behavior Survey were used (n = 26,951). Multivariate logistic regression was used to assess associations between the recent indoor tanning use and recently doing the following to lose weight: fasting for more than 24 hours; taking a pill, powder, or liquid without a doctor's consent; and vomiting or taking a laxative. RESULTS: Pooled data showed 23.3% of females reported indoor tanning within the past year; 6.5% of males did so as well. Adjusted multivariate results show that females who indoor tan were, on average, more likely to have fasted (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), taken a pill, powder, or liquid (OR, 2.4; 95% CI, 1.9-3.0), and vomited or taken a laxative to lose weight (OR, 1.4; 95% CI, 1.1-1.7) within the past 30 days than those who did not. Males who indoor tanned within the past year were, on average, more likely to have fasted (OR, 2.3; 95% CI, 1.7-3.1), taken a pill, powder, or liquid (OR, 4.4; 95% CI, 3.3-6.0), and vomited or taken a laxative to lose weight (OR, 7.1; 95% CI, 4.4-11.4) within the past 30 days. CONCLUSIONS: Significant associations between indoor tanning use and unhealthy weight control behaviors exist for both male and female adolescents, with a stronger association observed among males.

Hookah use among adolescents in the United States: results of a national survey.

INTRODUCTION: U.S. adolescents increasingly use alternative tobacco products (ATPs), including hookah. No study has previously assessed correlates of adolescent hookah use in a nationally representative sample. METHODS: Cross-sectional, nationally representative data of adolescents from the 2011 National Youth Tobacco Survey (NYTS) were used. Student demographics and their use of, exposure to, and beliefs about tobacco were examined as correlates of hookah use. RESULTS: Of adolescents nationwide, 7.3% reported ever trying hookah and 2.6% reported using hookah within the past month. Increasing age was associated with trying hookah, but not current hookah use. Sex was unassociated with hookah use. Asians were most likely to have tried hookah; Hispanics and those of another race reported greater current hookah use. Hookah use increased with perceived ease of access to and willingness to try tobacco. Students with a hookah user at home were more likely to have tried hookah and to currently use hookah. Current cigarette use was not associated with current hookah use (odds ratio [OR] = 1.3, 95% CI = 0.8-2.1), but was associated with trying hookah (OR = 1.5, 95% CI = 1.1-2.2). Non-cigarette tobacco use was associated with trying hookah (OR = 2.7, 95% CI = 2.1-3.5) and current hookah use (OR = 4.8, 95% CI = 2.7-8.7). CONCLUSIONS: A sizeable minority of U.S. adolescents use hookah, particularly those living with hookah users, those who use other ATPs, and those who perceive tobacco as easily accessible. Current cigarette use was not associated with current hookah use. Future studies assessing the dangers of hookah use and interventions to curb this emerging problem appear warranted.

Diverging racial trends in neonatal infantile hemangioma diagnoses, 1979-2006.

Nationally representative historical trends in neonatal infantile hemangioma (IH) diagnosis have not been previously assessed. Using the National Hospital Discharge Survey (NHDS), trends in IH diagnoses were assessed according to race and sex. Findings confirmed prior research that female and white newborns are more likely to be diagnosed with IH, and a statistically significant increase in IH diagnoses was observed in white, but not in nonwhite, infants.